5q-spinal muscular atrophy (5q-SMA) is a rare, autosomal recessive neuromuscular disease characterized by degeneration of motor neurons in the spinal cord and lower brainstem with progressive muscle atrophy, weakness, and paralysis. The incidence is 1 in 7-10,000 live births. 5q-SMA presents a wide range of phenotypes that are classified into five clinical groups depending on age of onset and maximum motor milestone achieved. SMA type 1 presents shortly after birth and before six months of age with inability to achieve independent sitting and limited life expectancy due to respiratory complications (high mortality rate by 2 years of age). In addition to the severe gross-motor and respiratory impairment, bulbar weakness and dysfunction represent an obstacle to the development of verbal skills in these patients. To date, very little is known about these functions in children with SMA 1. With the increasing number of long-term SMA 1 survivors worldwide thanks to the availability of new pharmacological treatments, it has become obvious that treated children show new phenotypes, presenting changes not only in motor and respiratory function, but also in other domains, including bulbar function, speech and communication development. We aim to investigate the evolution of bulbar function and speech/communication development in children with SMA type 1 treated with approved disease-modifying therapies through validate scales and questionnaires for the paediatric population. Additional neurophysiological and neuroimaging studies will be offered on an optional basis to further investigate the underlying brain electrical activity, and brain structural and functional organization. The information gathered would promote the definition of additional outcome measures capturing improvement at these levels. A better understanding of the development of these areas would help to plan SMA 1- tailored supportive programs provided by speech and language therapists, thus enhancing the current recommendations for management in SMA.
Study design: observational longitudinal study. In the first instance, this is intended as a single-centre pilot study with a total duration of 3 years. A larger longitudinal study in a wider national and international cohort will be planned according to preliminary results and insights from this pivotal study. The first appointment will be the screening visit. Initially the trial will be discussed, and informed consent will be obtained for participation in the trial. Information will be collected from the patient and their family including demographics, medical history and detail on medications used by the patient. The investigator will discuss and obtain information on feeding and nutritional support required by the patient, speech and language interventions in place including if they are an augmentative alternative communication user and/or eye tracking device user. After this the investigator will be able to confirm eligibility for the trial. The second visit is the baseline, during this a set of assessments will take place to establish the patients' baseline function. This will include a bulbar function assessment (speech and swallowing), a speech and communication assessment and a cognitive assessment (Thinking abilities; memory, language, reasoning and perception). The investigator will collect further data on respiratory function (breathing) and gross motor function (Muscle strength and abilities). The investigator will assess any adverse events which have occurred since the last visit including symptoms, signs, illness etc. There are further tests which could take place at this visit which are an optional part of the study these include event-related potentials, Brain scan (MRI) and additional communication tests. Patients will then be seen at 6 monthly intervals, at 6m, 12m, 18m, 24m, 30m and 36 months. At each of these appointments and changes to medications will be documented. The investigator will discuss and obtain information on feeding and nutritional support required by the patient, speech and language interventions in place including if they are an augmentative alternative communication user and/or eye tracking device user. Assessments which took place at baseline will be repeated including a bulbar function assessment (speech and swallowing), a speech and communication assessment and we will collect data on respiratory function (breathing) and gross motor function (muscle strength and abilities). Cognitive testing will occur at visits at 12, 24 and 36 months. At all visits the investigator will assess any adverse events which have occurred since the last visit including symptoms, signs, illness etc. If patients have decided to take part in additional cognitive testing, then this will occur at each 6 monthly visit. The month 36 visit will be the end of study visit so as well as the above will include repeat testing of the optional event-related potentials and brain scan (MRI).
Study Type
OBSERVATIONAL
Enrollment
30
Great Ormond Street Hospital
London, United Kingdom
RECRUITINGBulbar function - Changes from baseline
Paediatric-Functional Oral Intake Scale (p-FOIS/CEDAS) Min score( Worse) - Max score 6 (Better performance)
Time frame: Baseline, Visit Month 12, Month 24, and Months 36
Bulbar function
Paediatric-Functional Oral Intake Scale (p-FOIS/CEDAS) Min score 1( Worse) - Max score 6 (Better performance)
Time frame: Visit Month 6
Bulbar function
Paediatric-Functional Oral Intake Scale (p-FOIS/CEDAS) Min score 1 (Worse) - Max score 6 (Better performance)
Time frame: Visit Month 18
Bulbar function
Paediatric-Functional Oral Intake Scale (p-FOIS/CEDAS) Min score 1( Worse) - Max score 6 (Better performance)
Time frame: Visit Month 30
Speech and Communication - Changes from baseline
MacArthur-Bates Communicative Development Inventory (MCDI) - Words and Gestures or Words and Sentences For 8-18 month-olds looking at words and gestures, the following min score (worse performance) - max scores (better performance) exist: Phrases understood: 0/28 Vocabulary understood: 0/396 Vocabulary used: 0/396 Early gestures: 0/18 Later gestures: 0/45 Total gestures: 0/63 For 18-30 month-olds looking at words and sentences, the following min score (worse performance) - max scores (better performance) exist: Words produced = 0/680 Irregular words = 0/25 Overregularized words = 0/45 Sentence complexity = 0/37
Time frame: Baseline, Month 12, Month 24, and Months 36
Speech and Communication
MacArthur-Bates Communicative Development Inventory (MCDI) - Words and Gestures or Words and Sentences For 8-18 month-olds looking at words and gestures, the following min score (worse performance) - max scores (better performance) exist: Phrases understood: 0/28 Vocabulary understood: 0/396 Vocabulary used: 0/396 Early gestures: 0/18 Later gestures: 0/45 Total gestures: 0/63 For 18-30 month-olds looking at words and sentences, the following min score (worse performance) - max scores (better performance) exist: Words produced = 0/680 Irregular words = 0/25 Overregularized words = 0/45 Sentence complexity = 0/373
Time frame: Visit Month 6
Speech and Communication
MacArthur-Bates Communicative Development Inventory (MCDI) - Words and Gestures or Words and Sentences For 8-18 month-olds looking at words and gestures, the following min score (worse performance) - max scores (better performance) exist: Phrases understood: 0/28 Vocabulary understood: 0/396 Vocabulary used: 0/396 Early gestures: 0/18 Later gestures: 0/45 Total gestures: 0/63 For 18-30 month-olds looking at words and sentences, the following min score (worse performance) - max scores (better performance) exist: Words produced = 0/680 Irregular words = 0/25 Overregularized words = 0/45 Sentence complexity = 0/37
Time frame: Visit Month 18
Speech and Communication
MacArthur-Bates Communicative Development Inventory (MCDI) - Words and Gestures or Words and Sentences For 8-18 month-olds looking at words and gestures, the following min score (worse performance) - max scores (better performance) exist: Phrases understood: 0/28 Vocabulary understood: 0/396 Vocabulary used: 0/396 Early gestures: 0/18 Later gestures: 0/45 Total gestures: 0/63 For 18-30 month-olds looking at words and sentences, the following min score (worse performance) - max scores (better performance) exist: Words produced = 0/680 Irregular words = 0/25 Overregularized words = 0/45 Sentence complexity = 0/37
Time frame: Visit Month 30
Speech and Communication - Changes from baseline
Peabody Picture Vocabulary Test (PPVT)
Time frame: Baseline, Visit Month 6, Month 12, Month 18, Month 24, Month 30 and Months 36
Speech and Communication
Peabody Picture Vocabulary Test (PPVT) Age-based standard scores (M = 100, SD = 15). Minimum value of normal range is 85, maximum value of normal range is 115, higher score means better outcome.
Time frame: Visit Month 6
Speech and Communication
Peabody Picture Vocabulary Test (PPVT) Age-based standard scores (M = 100, SD = 15). Minimum value of normal range is 85, maximum value of normal range is 115, higher score means better outcome.
Time frame: Visit Month 18
Speech and Communication
Peabody Picture Vocabulary Test (PPVT) Age-based standard scores (M = 100, SD = 15). Minimum value of normal range is 85, maximum value of normal range is 115, higher score means better outcome.
Time frame: Visit Month 30
Speech and Communication - Changes from Baseline
Social Communication Questionnaire (SCQ) Minimum value is 0, maximum value is 39, higher score means worse outcome (The threshold varies depending on countries and researchers).
Time frame: Baseline, Month 12, Month 24, and Months 36
Speech and Communication
Social Communication Questionnaire (SCQ) Minimum value is 0, maximum value is 39, higher score means worse outcome (The threshold varies depending on countries and researchers).
Time frame: Visit Month 6
Speech and Communication
Social Communication Questionnaire (SCQ) Minimum value is 0, maximum value is 39, higher score means worse outcome (The threshold varies depending on countries and researchers).
Time frame: Visit Month 18
Speech and Communication
Social Communication Questionnaire (SCQ) Minimum value is 0, maximum value is 39, higher score means worse outcome (The threshold varies depending on countries and researchers).
Time frame: Visit Month 30
Cognitive function - Changes from baseline
Bayley Scales of Infant \& Toddler Development - Forth Edition Age-based standard scores (M = 100, SD = 15). Minimum value of normal range is 85, maximum value of normal range is 115, higher score means better outcome.
Time frame: Baseline, Month 12, Month 24, and Months 36
Cognitive function
Bayley Scales of Infant \& Toddler Development - Forth Edition Age-based standard scores (M = 100, SD = 15). Minimum value of normal range is 85, maximum value of normal range is 115, higher score means better outcome.
Time frame: Visit Month 6
Cognitive function
Bayley Scales of Infant \& Toddler Development - Forth Edition Age-based standard scores (M = 100, SD = 15). Minimum value of normal range is 85, maximum value of normal range is 115, higher score means better outcome.
Time frame: Visit Month 18
Cognitive function
Bayley Scales of Infant \& Toddler Development - Forth Edition Age-based standard scores (M = 100, SD = 15). Minimum value of normal range is 85, maximum value of normal range is 115, higher score means better outcome.
Time frame: Visit Month 30
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